1.
Elevated Homocysteine Concentrations Decrease the Antihypertensive Effect of Angiotensin-Converting Enzyme Inhibitors in Hypertensive Patients.
Qin, X, Li, Y, Sun, N, Wang, H, Zhang, Y, Wang, J, Li, J, Xu, X, Liang, M, Nie, J, et al
Arteriosclerosis, thrombosis, and vascular biology. 2017;(1):166-172
Abstract
OBJECTIVE We aimed to examine whether baseline homocysteine (Hcy) concentrations affect antihypertensive responses to enalapril treatment among previously untreated hypertensive patients (n=10 783) in the CSPPT (China Stroke Primary Prevention Trial). APPROACH AND RESULTS After a 3-week run-in treatment with a daily dose of 10 mg enalapril, eligible hypertensive patients were randomly assigned to a double-blind daily treatment of a tablet of either enalapril (10 mg) and folic acid (0.8 mg) or enalapril (10 mg) alone for a median of 4.5 years. After the 3-week treatment period with enalapril alone, the systolic blood pressure-lowering effect was significantly reduced by 1.39 (95% confidence interval 0.40-2.37) and 3.25 (95% confidence interval 1.98-4.52) mm Hg, respectively, in those with baseline Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001) as compared with those with Hcy concentration of <10 μmol/L. Similar results were observed after a 15-week treatment period with enalapril alone. After a median 4.5-year enalapril-based antihypertensive treatment period, compared with those with Hcy concentration of <10 μmol/L, the systolic blood pressure-lowering effect was still significantly reduced by 0.77 (95% confidence interval 0.01-1.53) and 1.70 (95% confidence interval 0.72-2.68) mm Hg, respectively, in those with Hcy concentrations of 10 to 15 and ≥15 μmol/L (P for trend <0.001). In addition, participants with higher baseline Hcy concentrations had persistently higher systolic blood pressure levels across the entire study treatment period. Similarly, baseline Hcy concentrations were inversely associated with diastolic blood pressure reduction during the short-term enalapril alone treatment. However, the inverse association between baseline Hcy and diastolic blood pressure reduction was attenuated and became insignificant after the long-term enalapril-based treatment period. CONCLUSIONS Elevated Hcy concentrations significantly decreased the antihypertensive effect of the short-term and long-term enalapril-based antihypertensive treatment in previously untreated hypertensive patients.
2.
Intron-2 conversion polymorphism of the aldosterone synthase gene and the antihypertensive response to angiotensin-converting enzyme inhibitors.
Yu, H, Lin, S, Zhang, Y, Liu, G
Journal of hypertension. 2008;(2):251-6
Abstract
BACKGROUND Aldosterone controls sodium balance and intravascular volume, and thus helps regulate blood pressure. Secretion of aldosterone is mainly regulated at the level of expression of the aldosterone synthase (CYP11B2) gene. The intron-2 conversion polymorphism of CYP11B2 was suggested to lead to overexpression of the gene, and may therefore have potential to predict the blood pressure response of patients with essential hypertension to angiotensin-converting enzyme inhibitors (ACEIs). OBJECTIVE To investigate the association between the intron-2 conversion polymorphism and the blood pressure response to ACEIs in a hypertensive cohort. DESIGN AND METHODS After a 2-week, single-blind, placebo run-in period, ACEIs were administered for 6 weeks to 509 patients with mild-to-moderate essential hypertension. The intron-2 conversion polymorphism was examined by polymerase chain reaction. RESULTS The IwIw genotype was observed in 106 patients (20.8%), the IwIc genotype in 251 patients (49.3%), and the IcIc genotype in 152 patients (29.9%). After 6 weeks of treatment the reductions in diastolic blood pressure were significantly greater in patients carrying IcIc or IwIc compared with IwIw genotypes (9.2 +/- 7.2 or 9.2 +/- 7.1 versus 6.4 +/- 6.6 mmHg, respectively; analysis of variance, P = 0.001). Stepwise multiple regression analysis showed that significant predictors of diastolic blood pressure reduction at 6 weeks were baseline diastolic blood pressure (P < 0.001), intron-2 conversion genotype (P = 0.006) and sex (P = 0.030). CONCLUSIONS The intron-2 conversion polymorphism was related to the diastolic blood pressure lowering response in hypertensive patients treated with ACEIs. Interindividual variation in the efficacy of antihypertensive medications may therefore be influenced by genetic factors.
3.
[The effect of perindopril in treatment of early diabetic nephropathy with normal blood pressure and microalbuminuria].
Yao, B, Hu, G, Li, Y, Liao, Z, Zhang, Y
Zhonghua nei ke za zhi. 2001;(12):826-8
Abstract
OBJECTIVE To study the effect of perindopril in decreasing the urinary albumin excretion rate (AER) and protecting the renal function in normotensive early diabetic nephropathy. METHODS 52 diabetic patients with AER between 20 to 200 microg/min, were treated with dietary regimen, oral antihyperglycemic agents or/ and insulin till their fasting blood glucose (FBG) was < 7.0 mmol/L and postprandial blood glucose (PBG) < 10.0 mmol/L. They were then divided randomly into two groups. Group A was a control group (25 cases), the patients were administered with placebo, group B was a treatment group (27 cases), the patients were administered with perindopril (4 mg/day) FBG, PBG, glycosylated haemoglobin A1c (HbA1c), AER, blood pressure (MAP) and blood creatinine (Cr) were examined immediately and 3, 6, 12 and 18 months after the treatment. RESULTS In group A, AER was significantly increased after 12 and 18 months than at beginning, they were (52.3 +/- 8.6) microg/min and (60.4 +/- 9.0) microg/min vs (44.2 +/- 6.8) microg/min (P < 0.05). In group B, after being treated with perindopril, AER estimated 3, 6, 12 and 18 months later were (20.3 +/- 5.6) microg/min, (22.1 +/- 6.1) microg/min, (21.3 +/- 5.9) microg/min and (20.8 +/- 5.7) microg/min respectively, all were significantly lower those that of group A in the same period (P < 0.05) and also significantly lower than those at the beginning (P < 0.05). CONCLUSION Perindopril has good effects in decreasing AER in normotensive early diabetic nephropathy and in protecting the renal function.